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Polyester-Based Dendrimer Nanoparticles Combined with Etoposide Have an Improved Cytotoxic and Pro-Oxidant Effect on Human Neuroblastoma Cells
Etoposide (ETO) is a cytotoxic drug that exerts its effect by increasing reactive oxygen species (ROS) production. Although ETO is widely used, fast metabolism, poor solubility, systemic toxicity, and multi-drug resistance induction all limit its administration dosage and its therapeutic efficiency....
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7022520/ https://www.ncbi.nlm.nih.gov/pubmed/31935872 http://dx.doi.org/10.3390/antiox9010050 |
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author | Alfei, Silvana Marengo, Barbara Domenicotti, Cinzia |
author_facet | Alfei, Silvana Marengo, Barbara Domenicotti, Cinzia |
author_sort | Alfei, Silvana |
collection | PubMed |
description | Etoposide (ETO) is a cytotoxic drug that exerts its effect by increasing reactive oxygen species (ROS) production. Although ETO is widely used, fast metabolism, poor solubility, systemic toxicity, and multi-drug resistance induction all limit its administration dosage and its therapeutic efficiency. In order to address these issues, a biodegradable dendrimer was prepared for entrapping and protecting ETO and for enhancing its solubility and effectiveness. The achieved dendrimer complex with ETO (CPX 5) showed the typical properties of a well-functioning delivery system, i.e., nanospherical morphology (70 nm), optimal Z-potential (−45 mV), good drug loading (37%), very satisfying entrapment efficiency (53%), and a remarkably improved solubility in biocompatible solvents. In regards to its cytotoxic activity, CPX 5 was tested on neuroblastoma (NB) cells with very promising results. In fact, the dendrimer scaffold and ETO are able to exert per se a cytotoxic and pro-oxidant activity on human NB cells. When CPX 5 is combined with ETO, it shows a synergistic action, slowly releasing the drug over time and significantly improving and protracting bioactivity. On the basis of these findings, the prepared ETO reservoir represents a novel biodegradable and promising device for the delivery of ETO into NB cells. |
format | Online Article Text |
id | pubmed-7022520 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-70225202020-03-09 Polyester-Based Dendrimer Nanoparticles Combined with Etoposide Have an Improved Cytotoxic and Pro-Oxidant Effect on Human Neuroblastoma Cells Alfei, Silvana Marengo, Barbara Domenicotti, Cinzia Antioxidants (Basel) Article Etoposide (ETO) is a cytotoxic drug that exerts its effect by increasing reactive oxygen species (ROS) production. Although ETO is widely used, fast metabolism, poor solubility, systemic toxicity, and multi-drug resistance induction all limit its administration dosage and its therapeutic efficiency. In order to address these issues, a biodegradable dendrimer was prepared for entrapping and protecting ETO and for enhancing its solubility and effectiveness. The achieved dendrimer complex with ETO (CPX 5) showed the typical properties of a well-functioning delivery system, i.e., nanospherical morphology (70 nm), optimal Z-potential (−45 mV), good drug loading (37%), very satisfying entrapment efficiency (53%), and a remarkably improved solubility in biocompatible solvents. In regards to its cytotoxic activity, CPX 5 was tested on neuroblastoma (NB) cells with very promising results. In fact, the dendrimer scaffold and ETO are able to exert per se a cytotoxic and pro-oxidant activity on human NB cells. When CPX 5 is combined with ETO, it shows a synergistic action, slowly releasing the drug over time and significantly improving and protracting bioactivity. On the basis of these findings, the prepared ETO reservoir represents a novel biodegradable and promising device for the delivery of ETO into NB cells. MDPI 2020-01-06 /pmc/articles/PMC7022520/ /pubmed/31935872 http://dx.doi.org/10.3390/antiox9010050 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Alfei, Silvana Marengo, Barbara Domenicotti, Cinzia Polyester-Based Dendrimer Nanoparticles Combined with Etoposide Have an Improved Cytotoxic and Pro-Oxidant Effect on Human Neuroblastoma Cells |
title | Polyester-Based Dendrimer Nanoparticles Combined with Etoposide Have an Improved Cytotoxic and Pro-Oxidant Effect on Human Neuroblastoma Cells |
title_full | Polyester-Based Dendrimer Nanoparticles Combined with Etoposide Have an Improved Cytotoxic and Pro-Oxidant Effect on Human Neuroblastoma Cells |
title_fullStr | Polyester-Based Dendrimer Nanoparticles Combined with Etoposide Have an Improved Cytotoxic and Pro-Oxidant Effect on Human Neuroblastoma Cells |
title_full_unstemmed | Polyester-Based Dendrimer Nanoparticles Combined with Etoposide Have an Improved Cytotoxic and Pro-Oxidant Effect on Human Neuroblastoma Cells |
title_short | Polyester-Based Dendrimer Nanoparticles Combined with Etoposide Have an Improved Cytotoxic and Pro-Oxidant Effect on Human Neuroblastoma Cells |
title_sort | polyester-based dendrimer nanoparticles combined with etoposide have an improved cytotoxic and pro-oxidant effect on human neuroblastoma cells |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7022520/ https://www.ncbi.nlm.nih.gov/pubmed/31935872 http://dx.doi.org/10.3390/antiox9010050 |
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